March 20, 2023
The National Center for Health Research (NCHR) appreciates the opportunity to submit public comments on use of medical device user fees collected by the Food and Drug Administration (FDA). NCHR is a non-profit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
For many years, we have advocated that device user fees be increased substantially to help support post-market surveillance of medical devices. This is essential for all devices, since only a small proportion of devices are proven safe or effective in clinical trials or other research prior to being cleared for market. In addition, recent research indicates that devices cleared on the basis of predicates that were subject to a Class I or Class II recall are especially likely to be recalled, and therefore should be carefully monitored as soon as they are on the market.1,2 Post-market surveillance is especially essential for high-risk devices, many of which were not studied in randomized, double blind, clinical trials.
If MDUFA funds are used for real-world evidence (RWE), it should focus on post-market surveillance. Moreover, we question the appropriateness of providing user fees that are intended to supplement FDA resources to other, non-government entities, given that device user fees are much lower than prescription drug user fees. Since user fees are intended to supplement government appropriations, providing user fees to non-government entities indirectly provides taxpayer money (appropriations) to these outside entities. The U.S. taxpayer deserves better.
The use of RWE to evaluate the safety and effectiveness of medical devices requires access to unbiased data of substantial numbers of patients that are demographically and medically similar to U.S. patients. Our comments below highlight specific considerations for the FDA regarding the use of premarket RWE when looking to external organizations beyond the scope of NEST.
Use of Registries
Device registries have been excellent sources of information in other countries, but there are numerous shortcomings for their use in the U.S, especially for pre-market use. Registries have the potential to include a matched control group to evaluate device effectiveness and safety, but are unlikely to make such comparisons. Research has indicated that registries can miss unmeasured confounding factors that may contribute to findings.3 For example, patients who receive a new device may have very different risk factors for adverse events than those who choose a different treatment or receive no treatment at all. That is especially true if the plan is to use registry data based on off-label uses of devices. These confounders can only be avoided through the use of a matched control group.
Access to information from registries is a major problem in the U.S., as registries are controlled by medical societies. These societies control the data collected as well as the data that they will make public to the FDA, other government agencies, or other researchers. For example, efforts to encourage surgeons to participate in registries have resulted in requiring limited information to be provided in the registry (i.e., simple data such as the number of revision surgeries). Implant registries often lack information about complications that would need to come from health professionals in other specialties, such as rheumatology or mental health. Additionally, these registries typically include little if any patient-reported outcomes, such as pain or quality of life, which are needed to evaluate outcomes that truly matter to patients.
Regardless of the source of funding, FDA should require access to all privacy-protected data from registries. However, it would be especially egregious if MDUFA funding is provided to entities that are gathering data that are not publicly available.
“Big Data” from billing records and electronic health records can be used to determine very serious adverse events, but have several limitations.4,5 It is not possible to determine if patients used devices as instructed, or complied with instructions to prevent infection or promote rehabilitation after they leave the medical facility. Additionally, when patients report pain or other complications, especially those that are subjective and relatively common, that information is not always included in billing records or EHR, making it difficult to accurately evaluate the frequency of adverse events. The use of billing data or EHR for pre-market data is therefore especially problematic, since it would presumably be based on devices used for a different purpose than those being considered for approval or clearance.
Transparency and Public Availability
Any data collected with MDUFA funding should be publicly available to the FDA and to other researchers. As noted earlier, MDUFA funds supplement appropriations, and if MDUFA funding is provided to non-government entities, that undermines the resources available through appropriations. That information should be made available to Congress and the public. In addition to requirements on accessibility and ownership, FDA should include requirements on transparency throughout the process and the selection of data items to be collected.
Increase Use of Unique Device Identifiers (UDI)
User fee funds should also be used to strengthen and enforce the use of UDI. There are several issues with UDIs. Currently, when a recall is posted to the FDA website, it does not always include the UDI. It is common for a manufacturer to print out dozens of pages of UDI numbers and FedEx them to the hospitals, instead of providing the information electronically. This involves some of the largest device companies as well as small device companies. Even today, the Center for Devices and Radiological Health (CDRH) list of COVID-19 devices that have been removed from the market does not include UDIs. Additionally, the UDI database itself is not being updated when a device is removed from commercial distribution. Any external organization receiving medical device user fees should be required to include UDI in all systems. UDI should be mandatory on adverse event reports since all classes of devices now require UDI.
Patient-Centered Outcomes that Include Benefits, Not Just Speed
As a nonprofit organization involved in the FDA’s MDUFA meetings, we learned first-hand that the goals of CDRH for user fees to improve patient safety were opposed by the device industry. That was of great concern to most if not all of the patient, consumer, and public health organizations involved in those meetings. The MDUFA V Commitment Letter can best be described as a contract where FDA is treated as the supplicant begging for funding, while industry clearly makes all the demands. The plan to provide MDUFA funds to non-FDA entities is unfair to U.S. taxpayers regardless of the goals; the fact that such funds will not provide unbiased and accurate information about devices based on RWE adds insult to injury.
1. Everhart, A., Sen, S., Stern, A., Zhu, Y., Karaca-Mandic P. (2023). Association Between Regulatory Submission Characteristics and Recalls of Medical Devices Receiving 510(k) Clearance. JAMA. 329(2):144–156. doi:10.1001/jama.2022.22974
2. Kadakia, K., Dhruva, S., Caraballo, C., Ross, J., Krumholz, H. (2023). Use of Recalled Devices in New Device Authorizations Under the US Food and Drug Administration’s 510(k) Pathway and Risk of Subsequent Recalls. JAMA. 329(2):136–143. doi:10.1001/jama.2022.23279
3. Nørgaard, M., Ehrenstein, V., & Vandenbroucke, J. P. (2017). Confounding in observational studies based on large health care databases: problems and potential solutions – a primer for the clinician. Clinical epidemiology, 9, 185–193. https://doi.org/10.2147/CLEP.S129879
4. Mourik, M., Duijn, P., Moons, K., et al. (2015). Accuracy of administrative data for surveillance of healthcare-associated infections: A systematic review. BMJ. https://bmjopen.bmj.com/content/5/8/e008424
5. Lawson EH, Louie R, Zingmond DS et al. (2012). A Comparison of Clinical Registry Versus Administrative Claims Data for Reporting of 30-Day Surgical Complications. Annals of Surgery. 256 (6): 973-981. https://pubmed.ncbi.nlm.nih.gov/23095667/